Disease relevance of CST6

• The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis [1].
• We here obtained the complete sequence of the human cystatin M/E gene (CST6), which provides a tool to investigate CST6 as a candidate gene in skin diseases characterized by abnormal cornification [1].
• This study thus provides the first evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression [2].
• CST6 indeed is expressed in the normal human breast epithelium, but little or not at all in breast carcinomas and breast cancer cell lines [2].
• Recombinant cystatin E was produced in a baculovirus expression system and isolated [3].
• Treatment of breast cancer cells with 5-aza-2'-deoxycytidine (5-Aza-CdR), reactivated the transcription of cystatin M [4].

High impact information on CST6

• In this study, we report a novel type of disease-causing mutation, an unstable 15- to 18-mer minisatellite repeat expansion in the putative promoter region of the CST6 gene [5].
• A strikingly high incidence of cystatin E clones in cDNA libraries from fetal skin epithelium and amniotic membrane cells (>0.5% of clones sequenced) indicates a protective role of cystatin E during fetal development [3].
• A new member of the human cystatin superfamily, called cystatin E, has been found by expressed sequence tag (EST) sequencing in amniotic cell and fetal skin epithelial cell cDNA libraries [3].
• Unlike other human low Mr cystatins, cystatin E is a glycoprotein, carrying an N-linked carbohydrate chain at position 108 [3].
• Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins [3].

Biological context of CST6

• To obtain insights into the molecular mechanism by which CST6 exhibits its pleiotropic effects on tumor cells, we compared global gene expression profiles in mock- and CST6-transfected human MDA-MB-435S cells [2].
• One down-regulated gene product, secreted autotaxin/lyso-phospholipase D, was of particular interest because its down-regulation by CST6 could explain most of CST6's effect on the breast cancer cells [2].
• We recently coined CST6 as a novel candidate tumor suppressor gene for breast cancer [2].
• Moreover, ectopic expression of CST6 in human breast cancer cells suppressed cell proliferation, migration, invasion, and orthotopic tumor growth [2].
• A rat homolog of human cystatin E/M was identified by differential display of transcripts induced during neuronal cell differentiation [6].

Anatomical context of CST6

• Additionally, two previously untested antibodies to molecules that have been found to be upregulated in papillary thyroid carcinoma (CST6 and EPS8) were also evaluated [7].
• Northern blot analysis revealed that the cystatin E gene is expressed in most human tissues, with the highest mRNA amounts found in uterus and liver [3].

Other interactions of CST6

• The level of cystatin E/M appears to be significantly associated with primary pleural tumours and cystatin F correlates with inflammatory processes of lung disorders [8].

References